tbuckley/cabot-search huggingface dataset:
Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia
Authors: Mattias Pilheden, Louise Ahlgren, Axel Hyrenius-Wittsten, Veronica Gonzalez-Pena, Helena Sturesson, Hanne Vibeke Hansen Marquart, Birgitte Lausen, Anders Castor, Cornelis Jan Pronk, Gisela Barbany, Katja Pokrovskaja Tamm, Linda Fogelstrand, Olli Lohi, Ulrika Norén-Nyström, Johanna Asklin, Yilun Chen, Guangchun Song, Michael Walsh, Jing Ma, Jinghui Zhang, Lao H. Saal, Charles Gawad, Anna K. Hagström-Andersson
Journal: HemaSphere (2022)

Infant acute lymphoblastic leukemia (ALL) with KMT2A -gene rearrangements ( KMT2A -r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A -r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A -r leukemia and included mutations in KRAS , NRAS , FLT3 , TP53 , PIK3CA , PAX5 , PIK3R1 , and PTPN11 , with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS . Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3 D835H or NRAS G13D/G12S mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A -r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
High Molecular and Cytogenetic Risk in Myelofibrosis Does Not Benefit From Higher Intensity Conditioning Before Hematopoietic Cell Transplantation: An International Collaborative Analysis
Authors: Nico Gagelmann, Rachel B. Salit, Thomas Schroeder, Anita Badbaran, Christina Rautenberg, Victoria Panagiota, Christine Wolschke, Felicitas Thol, Bruno Cassinat, Marie Robin, Michael Heuser, Hans Christian Reinhardt, Bart L. Scott, Nicolaus Kröger
Journal: HemaSphere (2022)

There is no direct evidence to recommend specific conditioning intensities in myelofibrosis undergoing allogeneic hematopoietic cell transplantation, especially in the molecular era. We aimed to compare outcomes of reduced intensity (RIC) or myeloablative conditioning (MAC) transplantation in myelofibrosis with molecular information. The study included 645 genetically annotated patients (with at least driver mutation status available), of whom 414 received RIC and 231 patients received MAC. The median follow-up time from transplantation was 6.0 years for RIC and 9.4 years for MAC. The 6-year overall survival rates for RIC and MAC were 63% (95% confidence interval [CI], 58%-68%) and 59% (95% CI, 52%-66%; P = 0.34) and progression-free survival was 52% (95% CI, 47%-57%) and 52% (95% CI, 45%-59%; P = 0.64). The 2-year cumulative incidence of nonrelapse mortality was 26% (95% CI, 21%-31%) for RIC and 29% (95% CI, 23%-34%) for MAC ( P = 0.51). In terms of progression/relapse, the 2-year cumulative incidence was 10% (95% CI, 5%-19%) for RIC and 9% (95% CI, 4%-14%) for MAC ( P = 0.46). Higher intensity conditioning did not seem to improve outcomes for higher-risk disease, according to mutational, cytogenetic, and clinical profile. In contrast, patients with reduced performance status, matched unrelated donors, and ASXL1 mutations appeared to benefit from RIC in terms of overall survival.
Viscoelastic Notch Signaling Hydrogel Induces Liver Bile Duct Organoid Growth and Morphogenesis
Authors: Muhammad Rizwan, Christopher Ling, Chengyu Guo, Tracy Liu, Jia‐Xin Jiang, Christine E. Bear, Shinichiro Ogawa, Molly S. Shoichet
Journal: Advanced Healthcare Materials (2022)

Abstract Cholangiocyte organoids can be used to model liver biliary disease; however, both a defined matrix to emulate cholangiocyte self‐assembly and the mechano‐transduction pathways involved therein remain elusive. A series of defined viscoelastic hyaluronan hydrogels to culture primary cholangiocytes are designed and it is found that by mimicking the stress relaxation rate of liver tissue, cholangiocyte organoid growth can be induced and expression of Yes‐associated protein (YAP) target genes could be significantly increased. Strikingly, inhibition of matrix metalloproteinases (MMPs) does not significantly affect organoid growth in 3D culture, suggesting that mechanical remodeling of the viscoelastic microenvironment—and not MMP‐mediated degradation—is the key to cholangiocyte organoid growth. By immobilizing Jagged1 to the hyaluronan, stress relaxing hydrogel, self‐assembled bile duct structures form in organoid culture, indicating the synergistic effects of Notch signaling and viscoelasticity. By uncovering critical roles of hydrogel viscoelasticity, YAP signaling, and Notch activation, cholangiocyte organogenesis is controlled, thereby paving the way for their use in disease modeling and/or transplantation.
NSUN2-Mediated mRNA m<b>5</b>C Modification Regulates the Progression of Hepatocellular Carcinoma
Authors: Dan Song, Ke An, Wenlong Zhai, Luyao Feng, Yingjie Xu, Ran Sun, Yueqin Wang, Yun-Gui Yang, Quancheng Kan, Xin Tian
Journal: Genomics Proteomics & Bioinformatics (2022)

RNA modifications affect many biological processes and physiological diseases. The 5-methylcytosine (m
Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial
Authors: Michael L Schilsky, Anna Czlonkowska, Massimo Zuin, David Cassiman, Carlos Twardowschy, Aurelia Poujois, Francisco de Assis A Gondim, Gerald Denk, Rubens G Cury, Peter Ott, Joanna Moore, Aftab Ala, Renata D'Inca, Eduardo Couchonnal-Bedoya, Koenraad D'Hollander, Nicolas Dubois, C Omar F Kamlin, Karl Heinz Weiss
Journal: The Lancet. Gastroenterology & hepatology (2022)
Synopsis of Blood Diseases
Journal: JAMA (1942)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Elements of Medical Treatment.
Journal: JAMA (1933)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Disseminating complex primary outcome results from a community-randomised trial to Zambian communities: lessons learned using a community dialogue approach in the HPTN 071 (PopART) trial
Authors: Musonda Simwinga, Rhoda Ndubani, Albertus Schaap, Daniel Ziba, Chiti Bwalya, Steve Belemu, Fredrick Ngwenya, Justin Bwalya, Kwame Shanaube, Graeme Hoddinott, Rhonda White, Peter Bock, Sarah Fidler, Richard Hayes, Janet Seeley, Helen Ayles, Virginia Bond
Journal: The Lancet HIV (2022)
Routine Establishment of Serial Lines of Hamster Embryo Cells Transformed by Adenovirus Type 12&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Robert R. Rafajko, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1967)

Whole hamster-embryo cells consistently underwent morphological alterations after 14–23 days in vitro when inoculated in suspension with adenovirus type 12, strain Huie, at multiplicities of 7 or more and incubated in a humidified 5% CO2 atmosphere at 37 C. Morphological changes were never observed when cells were incubated in the absence of 5% CO2. Altered cells were successfully cultivated for long periods and 12 serial lines were established in 12 attempts when medium NCTC 109 supplemented with 10% agamma calf serum was used. Attempts to establish serial lines on minimum essential medium in Earle's balanced salt solution with added serum were unsuccessful. Serial lines of hamster embryo cells transformed by adenovirus type 12 (ad-12) had the following inheritable characteristics: 1) small polygonal cells of uniform morphology; 2) accelerated growth rate; 3) loss of contact inhibition; 4) presence of ad-12 “T” antigen; and 5) transplantability into newborn and weanling hamsters. Virus could not be recovered from any cell line by conventional techniques. Of the 6 oncogenic ad-12 strains tested, only the prototype strain Huie was able to induce permanent morphological changes in hamster cells.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2015)

Convergence on the STAT3 Pathway in LymphomaCrescenzo and colleagues sequenced 155 ALK-negative anaplastic large cell lymphomas (ALCL), identifying oncogenic JAK1 or STAT3 mutations leading to constitutive activation of STAT3, also activated by tyrosine kinase fusions involving transcription factors NFKB2 or NCOR2 and tyrosine kinases ROS1 or TYK2.These findings underscore that mutated STAT3 proteins are potent transcriptional activators and that STAT3-mediated transformation requires modulation of numerous genes and can occur in the absence of JAK1/STAT3 mutations.The clinical outcome for patients with ALK-negative ALCL is dismal, but these findings, if validated in larger cohorts, provide the opportunity to selectively target the JAK/STAT3 pathway.The central role of STAT3 in human cancer also provides an opportunity for emphasis on drug development against this key pathway.(Image by Nephron courtesy of
MEDICAL LICENSURE EXAMINATIONS
Journal: JAMA (1942)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Oral Lesions in Pityriasis Rosea
Authors: John L. Kestel
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Oral lesions in pityriasis rosea have been described previously although they are relatively uncommon and few dermatologists have had the opportunity to see them. Oral involvement may occur more often in children than adults.<sup>1</sup>The eruption in the mouth, when it does occur, follows a course similar to that of the cutaneous involvement. In addition to areas of dermatitis, several instances of hemorrhagic lesions have been reported.<sup>2-4</sup>This report illustrates a typical example of this lesion, and describes the microscopic findings of the oral lesions. <h3>Report of a Case:—</h3> This 18-year-old Negro male experienced, a localized scaling area on the side of the neck followed one week later by smaller, similar lesions on the neck, lower face, chest, back, abdomen, and arms. Most of them were oval shaped, located in the lines of cleavage, and ranged from a few millimeters to several centimeters in diameter.
Intercellular Transfer of Toxic Components After Laser Irradiation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: May, James F., Rounds, Donald E., Cone, Clarence D.
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Intercellular Transfer of Toxic Components After Laser Irradiation Get access James F. May, James F. May Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald E. Rounds, Donald E. Rounds 3 3Address reprint requests to Dr. Donald E. Rounds, Pasadena Foundation for Medical Research, 99 N. El Molino Ave., Pasadena, Calif. 91101. Search for other works by this author on: Oxford Academic PubMed Google Scholar Clarence D. Cone Clarence D. Cone Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 46, Issue 3, March 1971, Pages 655–663, https://doi.org/10.1093/jnci/46.3.655 Published: 01 March 1971 Article history Received: 22 September 1970 Accepted: 25 November 1970 Published: 01 March 1971
Government must proceed with landmark anti-obesity regulations in England
Authors: Sarah Muir, Preeti Dhuria, Christina Vogel
Journal: BMJ (2022)

was meant to be a landmark date in food policy, with the implementation in England of world leading legislation to restrict the placement, promotion, and marketing of high fat, sugar, and salt (HFSS) products in shops and online. 1 Yet in May 2022 the government announced that the planned ban on volume based (multibuy) promotions of HFSS products-a core part of this novel legislation-was to be postponed for a year.The government blamed the delay on the cost of living crisis, 2 despite objections from the public health community and concrete evidence that such promotions increase spending on, and consumption of, these unhealthy food products. 3 4 In September 2022, this legislation was dealt a further blow, as it was reported that Liz Truss's government would be carrying out a review that could see these regulations scrapped in their entirety. 5This would have also put an end to restrictions on the placement of pre-packed HFSS products in prominent locations, such as store entrances, aisle ends, checkouts, and website homepages, which were still scheduled for 1 October 2022. 5We, like other health advocates, are delighted that this legislation is for now still going ahead, but whether the government will change course on its obesity strategy in the longer term remains unclear.
When I use a word . . . . Too much healthcare—self-assessment
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

Underconfidence and overconfidence are the Scylla and Charybdis of medical practice. Too much of the former and you will hesitate and overinvestigate; too much of the latter and you will misdiagnose and overtreat. Either way the patient suffers. The Dunning–Kruger effect supposedly predicts how good people are at self-assessment—those with little knowledge or competence overestimate their ability, while those who are highly competent underestimate it. However, although the reality of the effect has been widely accepted, several criticisms have been raised, including the small numbers studied, the problem of statistical regression to the mean, and the problem of the random noise that accompanies the measurement of self-assessment. In reality, although qualified experts are better at self-assessment than novices are, there is no strong tendency for individuals of all grades of competence to be overconfident in self-assessment and very few people (about 5%) are actually “unskilled and unaware of it,” as Kruger and Dunning originally put it.
Usefulness of the two-devices-in-one-channel technique for difficult bile duct intubation in patients without periampullary diverticulum
Authors: Takashi Kaneko, Kazuya Sugimori, Kazuki Endo, Masaki Nishimura, Yuichiro Tozuka, Haruo Miwa, Shin Maeda
Journal: Endoscopy (2022)

The two-devices-in-one-channel technique (2D-1C) has been reported as a useful method in cases of periampullary diverticulum [1] [2]. We experienced two cases in which 2D-1C was effective in patients without periampullary diverticulum, who presented with large oral protrusion and poor fixation of the papilla. These clinical features are among of the underlying causes of difficulties in bile duct cannulation [3].
Effective application of self-assembling peptide matrix with the gel immersion technique and red dichromatic imaging for hemostasis of postendoscopic sphincterotomy bleeding
Authors: Haruka Toyonaga, Tsuyoshi Hayashi, Risa Nakamura, Kosuke Iwano, Toshifumi Kin, Kuniyuki Takahashi, Akio Katanuma
Journal: Endoscopy (2022)

Endoscopic sphincterotomy is an essential procedure during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis or treatment of pancreaticobiliary disease; however, postendoscopic sphincterotomy bleeding occasionally occurs and is a potentially life-threatening adverse event [1]. Recently, a novel self-assembling peptide matrix (PuraStat; 3-D Matrix Europe SAS, France), which is approved for hemostasis in gastrointestinal endoscopic procedures, was launched [2]. Because of its characteristics, this product is not effective in achieving hemostasis of pooled blood, as the peptide matrix assembles when the solution comes into contact with body fluids. For effective hemostasis, the peptide matrix gel should be applied as close as possible to the bleeding point of the injured vessel wall. Herein, we report the effective application of PuraStat for hemostasis of postendoscopic sphincterotomy bleeding while securing an endoscopic field of view with the gel immersion technique [3] and red dichromatic imaging (RDI; Olympus, Japan) [4] [5] ([Video 1]).
Successful hemostasis of a parapapillary diverticular hemorrhage by the retroflexion technique in the descending part of duodenum
Authors: Kurato Miyazaki, Motohiko Kato, Motoki Sasaki, Teppei Masunaga, Atsushi Nakayama, Takanori Kanai, Naohisa Yahagi
Journal: Endoscopy (2022)

In endoscopic procedures, the retroflexion technique is often useful to overcome difficult situations [1] [2] [3] [4] [5]. Here, we report a successful hemostasis case of parapapillary diverticular hemorrhage by the retroflexion technique in the descending part of duodenum.
Breakthrough cannulation using “one forceps and one guidewire” technique in a patient with a Roux-en-Y anastomosis
Authors: Kook Hyun Kim, Sung Bum Kim
Journal: Endoscopy (2022)

A 67-year-old patient visited the emergency department with abdominal pain caused by a bile duct stone. He had previously undergone a total gastrectomy with Roux-en-Y anastomosis because of gastric cancer. His initial blood chemistry results were as follows: C-reactive protein 24.9 mg/dL; total bilirubin 3.1 mg/dL; alkaline phosphatase 74 IU/L, and γ-glutamyltransferase 395 IU/L. Abdominal computed tomography revealed a large stone in the common bile duct (CBD). Due to the Roux-en-Y anastomosis, a cap-fitted short-type single-balloon enteroscope (SIF-Y0004; Olympus Medical Systems, Tokyo, Japan) was used. However, the major papilla was unusually small. A series of attempts at biliary cannulation using an endoscopic retrograde cholangiopancreatography (ERCP) catheter (Boston Scientific, USA) with a preloaded guidewire were futile because the orifice was so small and flat ([Fig. 1]).
A tale of two ampullas: a rare anatomic anomaly captured on video during endoscopic retrograde cholangiopancreatography
Authors: Tamasha Persaud, Enad Dawod, Shawn Shah, Reem Z. Sharaiha, Kartik Sampath
Journal: Endoscopy (2022)

Most commonly the fusion of the bile duct (BD) and pancreatic duct (PD) gives rise to a single opening known as the ampulla of Vater. Ten to fifteen percent of individuals have separate openings, however in these cases the openings are typically within the same papilla, separated by a septum. Rarely, complete nonunion of the BD and PD occurs resulting in a double ampulla of Vater [1] [2]. This has been reported in approximately 0.18 % of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) [3]. This anatomic variant has been described in several case reports but, to our knowledge, has not been captured on video until this case.
Usefulness of texture and color enhancement imaging in peroral cholangioscopy
Authors: Yuki Tanisaka, Masafumi Mizuide, Akashi Fujita, Rie Shiomi, Takahiro Shin, Masanori Yasuda, Shomei Ryozawa
Journal: Endoscopy (2022)

The application of peroral cholangioscopy (POCS) has been reported to be useful for detailed inspection of patients with biliary stricture [1] [2]. We report a case of biliary stricture that had undergone POCS using texture and color enhancement imaging (TXI) and red dichromatic imaging (RDI) equipped in a new-generation image-enhanced endoscopy (IEE) system (EVIS X1; Olympus Medical Systems, Japan) [3].
Additional irrigation tube with therapeutic endoscope to aid gel immersion endoscopic submucosal dissection
Authors: Taro Iwatsubo, Yosuke Mori, Shinya Abe, Akitoshi Hakoda, Noriaki Sugawara, Kazuhiro Ota, Toshihisa Takeuchi
Journal: Endoscopy (2022)

Gel immersion endoscopy has several advantages including low pressure (to prevent patient discomfort) [1], easy implementation of hemostasis with clear visibility of the bleeding point [2] [3], a clear visual field, and the buoyancy effect during endoscopic submucosal dissection (ESD) [4] [5]. However, gel immersion endoscopy requires a specific device, the BioShield irrigator (US Endoscopy, Mentor, Ohio, USA) [4] [5], which combines the gel supply, device insertion, and aspiration line into one accessory channel. This arrangement interferes with the gel or the air during insertion and removal of endoscopic devices, and wastes gel in the channel collected by aspiration. To overcome these disadvantages, we developed a novel technique using a scope fitted with an easily available tube for gel supply, and we achieved successful esophageal ESD with it.